Novel bicycloalkane derivatives and the production thereof

ABSTRACT

Bicycloalkane derivatives of the formula ##STR1## WHEREIN N IS 1 OR 2, R 1  is lower alkyl, X is carbonyl or a free or etherified hydroxymethylene, and Y is --S--R 2 , --SO m  --R 2 , or ##STR2## wherein m is 1 or 2, R 2  is aryl or aralkyl, R 3  is hydrogen or lower alkyl, R 4  is phenyl optionally substituted with lower alkoxy or benzyloxy, and Z is nitro, lower alkanoyl, lower alkylsulfinyl, or lower alkylsulfonyl, are useful intermediates in the total synthesis of steroids. The compounds are prepared by reacting a corresponding compound lacking the CH 2  Y substituent with formaldehyde and a mercaptan or a sulfinic acid, followed if desired by oxidation and optional salt condensation.

REFERENCE TO COPENDING APPLICATIONS

This is a continuation-in-part of Application Ser. No. 317,549, filedDec. 22, 1972, now U.S. Pat. No. 4,008,253, whose disclosure isincorporated by reference.

BACKGROUND OF THE INVENTION

This invention relates to novel bicycloalkane derivates and to processesfor the preparation thereof.

Many efforts have been directed in recent years towards developingtotally synthetic techniques for the preparation of steroids. However,most of the processes and intermediates theretofore described have beenobtainable only in poor yields and with only a limited number of stablesubstituent groups. Because of the complex nature of steroid synthesis,a high premium is placed on regeospecific and stereospecific reactionswhich provide reaction products in good yields and relatively free fromdifficulty separable and analogues, which has been particularlytroublesome in the regeospecific alkylation of bicycloalkane derivativeson the unsaturated ring carbon atom adjacent a keto group (Z.G. Hajos etal, J.Org.Chem., 32,1967,3008 and Belgian Pat. No. 736.791).

We have found, that bicycloalkane derivatives can directly andregeospecifically be alkylated. The compounds thus obtained are veryvaluable intermediates for the total synthesis of steroids.

OBJECTS OF THE INVENTION

Accordingly, it is an object of this invention to provide novelbicycloalkane derivatives.

Another object of this invention is to provide a stereospecific processfor preparing bicycloalkane derivatives.

A further object of this invention is to provide compounds which areuseful intermediates in the synthesis of known steroids.

Upon further study of the specification and appended claims, furtherobjects and advantages of this invention will become apparent to thoseskilled in the art.

SUMMARY OF THE INVENTION

The above and other objects are attained in a chemical compound aspectof this invention by providing novel bicycloalkane derivatives ofFormula I ##STR3## wherein n is 1 or 2, R₁ is lower alkyl, X is carbonylor a free or etherified hydromethylene, and Y is --S--R₂, --SO_(m) --R₂,or ##STR4## wherein m is 1 or 2, R₂ is aryl, or aralkyl, R₃ is R₃ ishydrogen or lower alkyl, R₄ is phenyl or phenyl substituted with loweralkoxy or benzyloxy, and Z is nitro, lower alkanoyl, loweralkylsulfinyl, or lower alkylsulfonyl.

In a process aspect, the above compounds are obtained by reactingcorresponding compounds lacking the CH₂ Y group with formaldehyde and amercaptan or a sulfinic acid to form a thioether or a sulfone of FormulaI, and the thioether is optionally oxidized to a corresponding sulfoxideor sulfone. The thioether, sulfoxide or sulfone can be condensed with asalt of the formula ##STR5## wherein R₃, R₄ and X have theabove-indicated values and B⁺ is an alkali metal, alkaline earth metalor quaternary ammonium cation.

DETAILED DISCUSSION

Preferred compounds of Formula I in accordance with this invention arethose compounds which meet one or more of the following criteria:

a. Compounds of the general Formula I in which R₁ is methyl or ethyl;

b. Compounds of the general Formula I in which n is 1, including thoseof (a);

c. Compounds of the general Formula I in which Y is --S--R₂, preferablywherein R₂ is aryl, including each of (a) and (b);

d. Compounds of the general Formula I in which Y is SO_(m) --R₂,preferably those wherein R₂ is aryl and m is 2, including each of (a)and (b);

e. Compounds of the general Formula I in which Y is --C(Z) (R₃)R₄,including each of (a) and (b);

f. Compounds as in (e) wherein Z is nitro, including each of (a) and(b);

g. Compounds as in (e) wherein Z is alkanoyl of 2-4 carbon atoms,including each of (a) and (b);

h. Compounds as in (e) wherein Z is alkylsulfinyl of 1 to 4 carbonatoms, including each of (a) and (b);

i. Compounds as in (e) wherein Z is alkylsulfonyl of 1-4 carbon atoms,including each of (a) and (b);

j. Compounds of the general Formula I in which X is hydroxymethylene,including each of (a) through (i); and

k. Compounds of general Formula I in which X is hydroxymethyleneetherified by alkyl of 1 to 4 carbon atoms, including each of (a)through (i).

Lower alkyl groups R₁ and R₃ (in Formula I) are preferably alkyl groupsof 1-4 carbon atoms, e.g., methyl, ethyl, propyl, isopropyl, butyl andtert.-butyl. Especially preferred alkyl groups R₁ and R₃ are methyl andethyl.

Preferred R₂ groups are phenyl or naphthyl, optionally ring substitutedby one or more of lower alkyl of 1-4 carbon atoms, preferably methyl;lower alkoxy of 1-4 carbon atoms, preferably methoxy; halogen,preferably chlorine or bromine, or nitro. Suitable aryl and aralkyl R₂groups include but are not limited to phenyl, o--, m--, andp-methylphenyl, and α- or β-naphthyl.

When R₄ is a substituted phenyl group, R₄ is preferably phenylsubstituted by lower alkoxy of 1-4 carbon atoms.

Examples of suitable R₄ groups include but are not limited to thefollowing: ##STR6## wherein "Alkyl" is alkyl of 1-4 carbon atoms;"Halogen" is chlorine or bromine; and V₁, V₂, and V₃ are eachindependently hydrogen or alkoxy of 1-4 carbon atoms.

X can be a free or etherified hydroxymethylene group. Suitableetherified hydroxymethylene groups are preferably alkoxymethylene groupsor aralkoxymethylene groups of 1-10 carbon atoms in the alkoxy oraralkoxy group. Suitable alkoxy or aralkoxy groups include but are notlimited to methoxy, ethoxy, propyloxy, butyloxy, tert.-butyloxy,isopropyloxy, and benzyloxy.

The invention furthermore relates to a process for the preparation ofthe novel bicycloalkane derivatives of Formula I, characterized in thata compound of the general Formula II ##STR7## wherein n, X, and R₁ havethe same meanings as indicated in Formula I, is reacted withformaldehyde and a mercaptan or a sulfinic acid; the thioethers of thegeneral Formula I are oxidized, if desired, to the sulfoxides orsulfones of the general Formula I; and optionally the thioethers,sulfoxides or sulfones of general Formula I are condensed with a salt ofFormula III ##STR8## wherein Z, R₃, and R₄ have the above-indicatedvalues, and B⁺ is an alkali metal, alkaline earth metal or quaternaryammonium cation.

The thioether, sulfoxides, or sulfones optionally occurring asintermediate products are those of Formula Ia ##STR9## wherein n, R₁,R₂, and X have the above-indicated values and v is 0, 1 or 2.

The first reaction stage of the process of this invention is conductedby reacting the compounds of Formula II with formaldehyde andstereoregulating amount of a mercaptan or a sulfinic acid, generally1-10 mols and preferably 1-2 mols per mol of the compound of Formula IIin the case of a mercaptan, and correspondingly 1-10 mols, preferably1-2 mols in the case of a sulfinic acid.

Mercaptans suitable for conducting the process of the present inventioninclude but are not limited to alkyl and aryl mercaptans, e.g. methylmercaptan, ethyl mercaptan, propyl mercaptan, isopropyl mercaptan, butylmercaptan, amyl mercaptan, isoamyl mercaptan, hexyl mercaptan, heptylmercaptan, ocytl mercaptan, phenyl mercaptan, o--, m--, andp-thiocresol, benzyl mercaptan and α- or β-thionaphthol. Preferredsulfinic acids are aromatic sulfinic acids, e.g. benzene- or toluene-sulfinic acid. Sulfenic acids are not well suitable for this reactiondue to their instability.

In order to conduct the first reaction step, tertiary amines areemployed as catalysts generally 1-50 and preferably 1-20 mols per mol ofreactants. Suitable tertiary amines are trialkylamines, e.g.,trimethylamine, triethylamine, or diisopropylethylamine;trialkanolamines, e.g. triethanolamine; dialkylarylamines, e.g.dimethylaniline; and non-aromatic heterocyclic amines, e.g.N-methylpiperidine or N-methylmorpholine.

In case sulfinic acids are employed as reactants in the first step ofthis reaction, carboxylic acids, e.g. acetic acid, can be used as thecatalysts.

The formaldehyde required for the first reaction step can be utilized asan aqueous formaldehyde solution, as trioxymethylene, or preferably inthe form of paraformaldehyde.

If sulfinic acids are employed as reactants for the first process step,the reaction can also be conducted by first reacting the sulfinic acidswith formaldehyde to the corresponding hydroxymethylsulfones, and thencondensing the latter in the presence of tertiary amines with a compoundof Formula II.

For the first reaction step, the tertiary amine proper can be used asthe solvent. However, it is also possible to add further inert solventsto the reaction mixture. Examples in this connection are: aromatichydrocarbons, e.g. benzene, toluene, or xylene; chlorinatedhydrocarbons, e.g. methylene chloride, chloroform, carbon tetrachloride,tetrachloroethane, or chlorobenzene; ethers, e.g. diethyl ether,diisopropyl ether, dibutyl ether, tetrahydrofuran, dioxane, glycoldimethyl ether or diethylene glycol dimethyl ether; alcohols, e.g.methanol, ethanol, isopropanol, or butanol; or water.

The reaction can be effected at a reaction temperature of 20°-200° C.,preferably 50°-160° C.

It is surprising that the compounds of Formula II can be alkylatedselectively on the double bond with formaldehyde and mercaptans orsulfinic acids, for if this first reaction step is conducted in theabsence of a stereoregulating amount of mercaptans or sulfinic acids,the reaction no longer takes place selectively and a mixture of numerouscompounds is obtained.

The optional oxidation of the thio compounds to the sulfoxides orsulfones of general Formula I takes place in accordance withconventional operating methods, e.g. as described in Houben Weyl.Methoden der org. Chemie Vol. 9 (1955) 211 ff.

In this reaction, it is possible to employ various conventionaloxidizing agents. Suitable oxidation agents include but are not limitedto peracids, e.g. peracetic acid, perbenzoic acid, or m-chloroperbenzoicacid; hydrogen peroxide; quinones, e.g,2,3-dichloro-5,6-dicyanobenzoquinone; tetravalent to septavalentmetallic oxides or salts, e.g. lead (IV) oxide, manganese (IV) oxide,chromium (VI) oxide, cerium (IV) sulfate, potassium chromate, potassiumdichromate, potassium permanganate; oxidizing halogen compounds, e.g.iodine, sodium periodate, N-bromosuccinimide, or N-chlorosuccinimide,etc.

When using hydrogen peroxide or metallic oxides or salts for thisoxidation, it is advantageous to conduct the oxidation in the presenceof acids to maintain the pH of the reaction mixture at less than pH 6preferably pH 1-5. Suitable acids are mineral acids, e.g. hydrochloricor sulfuric acid, or lower carboxylic acids, e.g. acetic acid orpropionic acid.

Solvents used for this reaction are protonic as well as aprotic inertsolvents. Suitable solvents include but are not limited to water; lowercarboxylic acids, e.g. acetic acid or propionic acid; tertiary alcohols,e.g. tert.-butanol; ketones, e.g. acetone, methyl ethyl ketone, orcyclohexanone; ethers, e.g. diethyl ether, diisopropyl ether,tetrahydrofuran, dioxane, or glycol dimethyl ether, hydrocarbons, e.g.benzene or toluene; and chlorinated hydrocarbons, e.g., methylenechloride, chloroform, carbon tetrachloride, tetrachloroethane orchlorobenzene.

By using, for the oxidation of the thioethers, 2 equivalents ofoxidizing agent per mol of thioether, the sulfoxides of general FormulaI are obtained; by using the oxidizing agent in an excess, thecorresponding sulfones are produced.

The optional condensation of the thioether, sulfoxide or sulfone withsalts of Formula III can be conducted by producing the salt from thecorresponding compound of Formula IV ##STR10## wherein Z, R₃, and R₄have the above-indicated values, by reaction with a suitable base in aninert solvent, followed by treating the thus-formed salt with thethioether, sulfoxide, or sulfone.

Alternatively, this reaction stage can be effected by simultaneouslyreacting the thioether, sulfoxide, or sulfone, with the compound ofFormula IV and with the suitable base in an inert solvent. Suitablebases for this reaction step are those customarily employed in saltformation of compounds of Formula IV, preferably the hydrides,alcoholates, or amides of the alkali or alkaline earth metals, e.g.sodium hydride, calcium hydride, sodium amide, sodium ethylate,potassium tert.-butylate; or quaternary ammonium bases, e.g.tetramethylammonium hydroxide or trimethylbenzylammonium hydroxide. Thisreaction step is preferably conducted by employing 0.1 - 2 mols of thebase, preferably 0.5 - 1.2 mols of base per mol of the compound ofFormula IV.

This reaction step is effected in a solvent which is inert with respectto the reactants under the existing conditions. Suitable solventsinclude but are not limited to hydrocarbons, e.g. cyclohexane, benzene,or toluene; ethers, e.g. diethyl ether, diiosopropyl ether, dibutylether, tetrahydrofuran, dioxane, or glycol dimethyl ether; polar aproticsolvents, e.g. dimethylformamide, acetonitrole, N-methylpyrrolidone, ordimethyl sulfoxide; alcohols, e.g. ethanol, butanol, tert.-butanol, orisopropanol; etc.

The condensation is preferably conducted at a reaction temperature ofbetween 20° and 120° C.

It is surprising to a person skilled in the art that the thioethers,sulfoxides, or sulfones of Formula I can be condensed with the salts ofFormula III, and that it is possible to obtain in this reaction thebicycloalkane derivatives of the general Formula Ib in good yields:##STR11## wherein n, X, Z, R₁, R₃, and R₄ have the same meanings as inFormula I. This is unexpected because thioethers, sulfoxydes andsulfones are in general very stabel compounds and it was not known, thatthese compounds may undergo such condensation reactions.

Condensation of the compounds of Formula III with the sulfoxides orsulfones of Formula Ia can be conducted under substantially milderreaction conditions than are required for effecting condensation withthe corresponding thioethers of Formula Ia. Therefore, it is usuallyadvantageous to condense the compounds of Formula III, wherein R₃ isalkyl, with sulfoxides or sulfones. On the other hand, the condensationof benzyl compounds of Formula III, with Z meaning an alkylsulfonylgroup, is preferably conducted with the use of thio compounds of FormulaIa.

The bicycloalkane derivatives of Formula Ib are valuable intermediateswhich are particularly suitable for the total synthesis of steroids.

Thus, it is possible, for example, to hydrogenate the double bondpresent in the bicycloalkane ring, and to eliminate the substituent Z.

In the compounds of Formula Ib wherein the substituent R₄ is analkoxycarbonyl group or an optionally substituted acyl group, thesubstituent Z can be eliminated using various techniques apparent tothose skilled in the art. For example, nitrile or alkoxycarbonyl Zgroups can be saponified, and the thus-formed β-ketocarboxylic acids canbe decarboxylated. Lower alkanoyl groups can be eliminated under theconditions customary for the keto splitting of β-diketones. Loweralkylsulfinyl and lower alkylsulfonyl Z groups can be eliminated by theRaney nickel desulfuration method. The thus-obtained compounds and theirfurther conversion into steroids are conventional.

The compounds of general Formula Ib, wherein R₄ is an optionallysubstituted phenyl residue are 9,10-seco-1,3,5(10),8(14)-estratetraenederivatives. These compounds can be hydrogenated in a conventionalmanner to the corresponding 9,10-seco-1,3,5(10)-estratrienes which canthen be cyclized in a manner known per se to the corresponding1,3,5(10)-estratriene derivatives. Subsequently, the substituent Zpresent in the 6-position of the estratriene can be eliminated in aconventional manner.

Thus, for example, the 6-nitro steroids can be converted into thecorresponding 6-keto steroids by means of the Nef reaction; the ketogroup of these steroids can be eliminated by hydrogenation, Clemmensenreduction, or equivalent methods.

The lower alkylsulfinyl groups or lower alkylsulfonyl groups present inthe 6-position can be eliminated, for example, by Raney nickeldesulfuration.

The 6-acyl steroids can be converted into the corresponding esters, forexample, with the aid of the Bayer-Villiger rearrangement.

Nitrile or alkoxycarbonyl groups present in the 6-position can beconverted, optionally after saponification, into 6-amino groups by meansof Hofmann degradation or equivalent methods; the amino groups can thenbe eliminated by means of hydrogenation.

The following examples serve for explaining the process of the presentinvention.

Without further elaboration, it is believed that one skilled in the artcan, using the preceding description, utilize the present invention toits fullest extent. The following preferred specific embodiments are,therefore, to be construed as merely illustrative, and not limitative ofthe remainder of the disclosure in any way whatsoever. The temperaturesherein are set forth in uncorrected degrees Celsius; unless otherwiseindicated, all parts and percentages are given by weight.

EXAMPLE 1

3.0 g. of 7aβ-methyl-5,6,7,7a-tetrahydroindane-1,5-dione is mixed with30 ml. of ethanol, 2.52 ml. of thiophenol, 1.6 ml. of triethanolamine,and 2 ml. of 30% strength formaldehyde solution; the reaction mixture isheated under reflux for 16 hours. Then, the mixture is poured into asolution, heated to 50°, of 20 g. of lead(II) acetate in 150 ml. of 50%aqueous ethanol. After about 30 minutes, the thus-separated leadmercaptide is filtered off and the filtrate concentrated by evaporationin vacuo. The remainder is distributed between water and ethyl acetate,the organic phase is washed neutral with water and dried with sodiumsulfate, thus obtaining 4.94 g. of7aβ-methyl-4-(phenylthio-methyl)-5,6,7,7a-tetrahydroindane-1,5-dione asan oil which melts, after recrystallization from diisopropyl ether, at93°-96°; yield: 3.2 g. [α]_(D) = +214° (1% = chloroform); ε₂₅₀ = 14,000;IR: 5.75 μ, 6.0 μ.

EXAMPLE 2

5.55 g. of 1β-tert.-butoxy-7aβ-methyl-5,6,7,7a-tetrahydroindan-5-one,2.75 ml. of phenyl mercaptan, and 0.75 g. of paraformaldehyde aredissolved in 8.5 ml. of triethanolamine and heated to 110° for 16 hours.The dark mixture is poured into 25 ml. of 1N sodium hydroxide solutionand extracted with ether; the ether phase is washed neutral, dried withsodium sulfate, and the solvent removed under vacuum. The yield of 8.6g. of a crude product in the form of a yellow oil is dissolved inethanol, thus producing 5.2 g. of crystalline1β-tert.-butoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5one.From the mother liquor, another 2.5 g. of product can be obtained afterconcentration. The total yield is 7.7 g. of this compound, m.p.103°-106°. [α]_(D) ²⁰ = +43° (chloroform; c = 1%) ε₂₅₃ = 14,000.

The same reaction can also be conducted by using, in place oftriethanolamine, a mixture of triethylamine and ethanol.

EXAMPLE 3

0.83 g. of 1β-hydroxy-7aβ-methyl-5,6,7,7a-tetrahydroindan-5-one, 0.55ml. of phenyl mercaptan, and 0.15 g. of paraformaldehyde are dissovledin 1.7 ml. of triethanolamine and heated to 110° for 8 hours. Themixture is then mixed with 5 ml. of 1N sodium hydroxide solution,extracted with ether, the ether phase washed neutral with sodiumchloride solution, and dried with sodium sulfate. After concentratingthe ether phase under vacuum, 1.25 g. of1β-hydroxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-oneis obtained as a crude product. The latter can be purified by means of asilica gel column and yields an oily product in the pure form with thephysical data: [α]_(D) ²⁰ = +34° (chloroform; c = 1%); ε₂₅₁ = 13,500.

EXAMPLE 4

0.86 g. of1β-tert.butoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-oneis dissolved in 15 ml. of dimethoxyethane, and a solution of 60 mg. ofsodium hydride in 1.5 ml. of ethyl acetoacetate is added thereto. Thereaction mixture is heated for 24 hours under reflux, is then taken upin 20 ml. of chloroform, and extracted with 10 ml. of 1N sodiumhydroxide solution and then with water. The organic phase is dried withsodium sulfate. The residue is purified on sillca gel by means ofchromatography, thus obtaining 0.60 g. of1β-tert.butoxy-7aβ-methyl-4-(3'-oxo-2'-ethoxycarbonylbutyl)-5,6,7,7a-tetrahydroindan-5-oneas a syrupy liquid; [α]_(D) = 0° (1% = chloroform); UV: ε₂₅₀ = 11,800,after the addition of 1N sodium hydroxide solution: ε₂₅₀ = 9,800,shoulder at 285 nm. IR bands at 5.75, 5.80, and 6.0 μ.

EXAMPLE 5

0.86 g. of1β-tert.-butoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-oneis dissolved in 15 ml. of dimethoxyethane. A solution of 60 mg. ofsodium hydride in 1 ml. of diethyl malonate is added thereto, and thereaction mixture is heated under reflux for 24 hours, taken up in 20 ml.of chloroform, and extracted with 10 ml. of 1N sodium hydroxide solutionand with water. The organic phase is dried with sodium sulfate and theresidue chromatographed on silica gel, thus producing 0.68 g. of pure1β-butoxy-7aβ-methyl-4-(2',2'-bisethoxycarbonylethyl)-5,6,7,7a-tetrahydroindan-5-oneas a light-yellow oil. ε₂₄₈ = 11,200; IR bands at 5.80 and 6.00 μ;[α]_(D) ²⁰ = +22° (chloroform; c = 1%).

EXAMPLE 6

1.25 g. of1β-trimethylacetoxy-7aβ-methyl-5,6,7,7a-tetrahydroindan-5-one, 0.6 ml.of phenyl mercaptan, and 0.15 g. of paraformaldehyde are dissolved in 2ml. of triethanolamine and agitated for 16 hours at 110° under anitrogen atmosphere. The reaction mixture is worked up as described inExample 3. The crude product (2.2 g.) is chromatographed on silica gel,thus obtaining 1.38 g. of pure1β-trimethylacetoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-one.The substance is oily. ε₂₄₉ = 13,700; IR bands at 5.75 and 6.02 μ.

EXAMPLE 7

0.9 g. of1,1-(2',2'-dimethylpropylenedioxy)-7aβ-methyl-5,6,7,7a-tetrahydroindan-5-one,0.6 of phenyl mercaptan, and 0.15 g. of paraformaldehyde are dissolvedin 2 ml. of triethanolamine and agitated for 16 hours at 110° undernitrogen. The reaction mixture is worked up and chromatographed asdisclosed in Example 3, thus producing from 2.6 g. of crude product 1.5g. of pure1,1-(2',2'-dimethylpropylenedioxy)-7aβ-methyl-4(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-onewhich, when recrystallized from diisopropyl ether, has a melting pointof 73°-74°. ε₂₅₁ = 15,400.

EXAMPLE 8

a. 5.0 g. of pure 7aβ-ethyl-5,6,7,7a-tetrahydroindane-1,5-dione isheated in 100 ml. of benzene with 10 g. of neopentyl glycol and 20 mg.of p-toluenesulfonic acid under reflux on a water trap for 2 hours.After chromatography on silica gel, 1.5 g. of1,1-(2',2'-dimethylpropylenedioxy)-7aβ-ethyl-5,6,7,7a-tetrahydroindane-5-oneis obtained. ε₂₅₀ = 14,000.

b. 1.06 g. of1,1-(2',2'-dimethylpropylenedioxy)-7aβ-ethyl-5,6,7,7a-tetrahydroindan-5-one,0.5 ml. of thiophenol, and 0.12 g. of paraformaldehyde are heated in 1.6ml. of triethanolamine to 110° for 16 hours. The reaction mixture isworked up and chromatographed as described in Example 3. From 1.53 g. ofcrude product, one obtains 0.91 g. of pure1,1-(2',2'-dimethylpropylenedioxy)-7aβ-ethyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-one.ε₂₅₁ = 13,800; IR band at 6.03 μ.

EXAMPLE 9

a. 6.0 g. of 8aβ-methyl-3,4,8,8a-tetrahydro1,6[2H,7H]-naphthalenedioneis dissolved in 100 ml. of benzene and heated under reflux with 12 g. ofneopentyl glycol and 20 mg. of p-toluenesulfonic acid for 45 minutes,the thus-formed water being separated. After chromatography on silicagel, 1.8 g. of1,1-(2',2'-dimethylpropylenedioxy)-8aβ-methyl-1,2,3,4,8,8a-hexahydro-6[7H]-naphthalenoneis obtained, m.p. 98°-101°. ε₂₄₄ = 11,200.

b. 1.32 g. of1,1-(2',2'-dimethylpropylenedioxy)-8aβmethyl-1,2,3,4,8,8a-hexahydro-6[7H]-naphthalenone,0.6 ml. of phenyl mercaptan, and 0.15 g. of paraformaldehyde are heatedin 2 ml. of triethanolamine to 110° for 16 hours. The reaction mixtureis worked up and chromatographed analogously to Example 3. From 2.0 g.of a crude product, one obtains 1.23 g. of pure1,1-(2',2'-dimethylpropylenedioxy)-8aβ-methyl-5-(phenylthiomethyl)-1,2,3,4,8,8a-hexahydro-6[7H]-naphthalenone.ε₂₄₅ = 11,000. IR band at 6.0 μ.

EXAMPLE 10

1.11 g. of 1β-tert.-butoxy-7aβ-methyl-5,6,7,7a-tetrahydroindan-5-one,1.0 ml. of 1-hexyl mercaptan, and 0.3 g. of paraformaldehyde aredissolved in 2 ml. of triethanomaine and heated to 110° for 20 hours.The mixture is worked up and chromatographed as described in Example 3,thus producing, from 1.6 g. of a crude product, 1.1 g. of pure1β-tert.-butoxy-7aβmethyl-4-(1'-hexylthiomethyl)-5,6,7,7a-tetrahydroindan-5-oneas an oil. ε₂₅₀ = 12,700. IR band at 6.0 μ.

EXAMPLE 11

1.11 g. of 1β-tert.-butoxy-7aβ-methyl-5,6,7,7a-tetrahydroindan-5-one,1.0 ml. of 3-hexyl mercaptan, and 0.3 g. of paraformaldehyde aredissolved in 2 ml. of triethanolamine and heated to 110° for 20 hours.The reaction mixture is worked up and chromatographed as disclosed inExample 3, thus obtaining, from 1.5 g. of a crude product, 1.1 g. ofpure1β-tert.-butoxy-7aβ-methyl-4-(3'-hexylthiomethyl)-5,6,7,7a-tetrahydroindan-5-oneas an oil. ε₂₅₀ = 12,500. IR band at 6.0 μ.

EXAMPLE 12

0.56 g. of1β-tert.-butoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7-a-tetrahydroindan-5-oneis dissolved in 10 ml. of dimethoxyethane. A solution of 1.0 ml. ofacetylacetone and 60 mg. of sodium hydride in 5 ml. of dimethoxyethaneis added thereto, and the reaction mixture is refluxed for 24 hours andthen worked up as indicated in Example 4. A crude yield of 0.6 g. isobtained and chromatography on silica gel results in 0.35 g. of1β-tert.-butoxy-7aβ-methyl-4-(3'-oxo-2'-acetylbutyl)5,6,7,7a-tetrahydroindan-5-one as an oil. IR bands at 5.75 and 6.03 μ;ε₂₄₉ = 11,300; [α]_(D) ²⁰ =+14° (chloroform; c = 1%).

EXAMPLE 13

0.86 g. of1β-tert.-butoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-oneis dissolved in 15 ml. of ethylene glycol dimethyl ether, and a solutionof 60 mg. of sodium hydride in 1 g. of the ethyl ester of7-chloro-3-oxo-6-octylenic acid is added to the reaction mixture and thelatter stirred for 16 hours under reflux. The mixture is worked up andchromatographed as set forth in Example 4. From 1.6 g. of crude product,one obtains 0.75 g. of pure1β-tert.-butoxy-7aβmethyl-4-(7'-chloro-3'-oxo-2'-ethoxycarbonyl-6-octenyl)-5,6,7,7a-tetrahydroindan-5-onein the form of an oil. ε₂₄₈ = 10,900; ε₃₁₁ = 1,360. IR bands at 5.75,5.82, and 6.0 μ.

EXAMPLE 14

0.86 g. of1β-tert.-butoxy-7a-β-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-oneand 1 ml. of 7,7-ethylenedioxy-3-oxo-octanoic acid ethyl ester, as wellas 60 mg. of sodium hydride are dissolved in 15 ml. of ethylene glycoldimethyl ether and heated under reflux for 16 hours. The mixture isworked up and chromatographed as disclosed in Example 4, thus obtaining,from 1.5 g. of crude product, 0.68 g. of pure1β-tert.-butoxy7β-methyl-4-(7',7'-ethylenedioxy-3'-oxo-2'-ethoxycarbonyloctyl)-5,6,7,7a-tetrahydroindan-5-onein the form of an oil.

ε₂₄₉ = 10,800; ε₃₁₀ = 1,100. IR bands at 5.75, 5.80, and 6.0 μ. [α]_(D)²⁰ =+6° (chloroform; c = 1%).

EXAMPLE 15

0.75 g. of1β-trimethylacetoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-one,1 ml. of diethyl malonate, and 60 mg. of sodium hydride are dissolved in15 ml. of ethylene glycol dimethyl ether and refluxed for 20 hours. Themixture is worked up and chromatographed as set forth in in Example 4,thus producing, from 1.5 g. of a crude product, 0.57 g. of pure, oily1β-trimethylacetoxy-7aβ-methyl-4-(2',2'-bisethoxycarbonylethyl)-5,6,7,7a-tetrahydroindan-5-one.ε₂₄₄ = 14,100. IR bands at 5.75 and 6.0 μ.

EXAMPLE 16

0.75 g. of1,1-(2',2'-dimethylpropylidenedioxy)-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-one,1 ml. of ethyl acetoacetate, and 60 mg. of sodium hydride are dissolvedin 15 ml. of ethylene glycol dimethyl ether and refluxed for 24 hours.The reaction mixture is worked up and chromatographed analogously toExample 4, thus obtaining, from 1.5 g. of crude products, 0.35 g. ofpure1,1-(2',2'-dimethylpropylenedioxy)-7aβ-methyl-4-(3"-oxo-2"-ethoxycarbonylbutyl)-5,6,7,7a-tetrahydroindan-5-onein the form of an oil.

ε₂₅₀ = 10,100. IR bands at 5.75, 5.80, and 6.0 μ.

EXAMPLE 17

0.86 g. of1β-tert.-butoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-one,1 ml. of the ethyl ester of cyanoacetic acid, and 60 mg. of sodiumhydride and dissolved in 15 ml. of ethylene glycol dimethyl ether andrefluxed for 24 hours. The reaction mixture is worked up andchromatographed as described in Example 4, thus obtaining, from 1.2 g.of crude product, 0.59 g. of pure, oily1β-tert.-butoxy-7aβ-methyl-4-(2'-ethoxycarbonyl-2'-cyanoethyl)-5,6,7,7a-tetrahydroindan-5-one.ε ₂₄₉ = 10,600. IR bands at 5.75 and 6.0 μ.

EXAMPLE 18

0.86 g. of1β-tert.-butoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-one,1 g. of methylsulfonyl-2-propanone, and 60 mg. of sodium hydride overare refluxed in 15 ml. of ethylene glycol dimethyl ether for 20 hours.The mixture is worked up and chromatographed as indicated in Example 4,thus producing, from 1.5 g of crude product, 0.5 g. of pure1β-tert.-butoxy-7aβ-methyl-4-(2'-methylsulfonyl-3'-oxobutyl)-5,6,7,7-a-tetrahydroindan-5-one.ε₂₅₀ = 11,100. IR bands at 5.8 and 6.0 μ.

EXAMPLE 19

0.86 g. of1β-tert.-butoxy-7aβ-methyl-4-(1'-hexylthiomethyl)-5,6,7,7a-tetrahydroindan-5-one,1 ml. of diethyl malonate, and 60 mg. of sodium hydride are dissolved in15 ml. of ethyl glycol dimethyl ether and refluxed for 20 hours. Thereaction mixture is worked up and chromatographed as described inExample 4, thus obtaining, from 1.3 g. of crude product, 0.5 of pure1β-tert.-butoxy-7aβ-methyl-4-(2',2'-bisethoxycarbonylethyl)-5,6,7,7a-tetrahydroindan-5-onein the form of an oil. ε₂₄₈ = 11,200. IR bands at 5.80 and 6.0 μ.[α]_(D) ²⁰ = +22° (chloroform; C = 1%).

EXAMPLE 20

1.72 g. of1β-tert.-butoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-oneis dissolved in 30 ml. of acetic acid, and, at room temperature, 0.7 ml.of 30% hydrogen peroxide is added thereto. Then, water is admixed to thereaction solution, and the latter is extracted with chloroform, and thechlorofom phase is washed out with 2N aqueous sodium hydroxide solutionand water. After drying the solution, the solvent is distilled off, theresidue is recrystallized from ether, and 1.1 g. of1β-tert.-butoxy-7aβ-methyl-4-(phenylsulfinylmethyl)-5,6,7,7a-tetrahydroindan-5-oneis thus obtained, m.p. 121°-125°. [α]_(D) ²⁰ = +186° (chloroform; c =1%).

EXAMPLE 21

0.86 g. of1β-tert.-butoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-one is dissolved in 10 ml. of dimethoxyethane, and, at 0°, 0.55 ml. of40% peracetic acid is added thereto dropwise, dissolved in 10 ml. ofdimethoxyethane. The mixture is worked up as described in Example 20,thus obtaining 0.75 g. of1β-tert.-butoxy-7aβ-methyl-4-(phenylsulfinylmethyl)-5,6,7,7a-tetrahydroindan-5-one,m.p. 122°-125°.

EXAMPLE 22

0.34 g. of1β-tert.-butoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-oneis dissolved in 5 ml. of dimethoxyethane and 2 ml. of water, and 0.2 g.of N-bromosuccinimde is added thereto, dissolved in 5 ml. ofdimethoxyethane, under agitation. The reaction mixture is worked upanalogously to Example 20, thus producing 0.28 g.of1β-tert.-butoxy-7aβ-methyl-4-(phenylsulfinylmethyl)-5,6,7,7a-tetrahydroindan-5-one,m.p. 121°-124°.

EXAMPLE 23

8.60 g. of1β-tert.-butoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-oneis dissolved in 200 ml. of ether and, at room temperature, mixed with9.0 of m-chloroperbenzoic acid, dissolved, in 150 ml. of ether. Thereaction mixture is allowed to stand for 10 minutes, and then thesolvent is exhaustively distilled off under vacuum. The residue is takenup in a small amount of methanol and 50 ml. of saturated aqueous sodiumbicarbonate solution, and the mixture is agitated for 15 minutes. Then,the ether phase is separated, dried with sodium sulfate, and the solventis distilled off. The residue is taken up in diisopropyl ether, cooledto 0°, and 7.92 g. of1β-tert.-butoxy-7aβ-methyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-oneis thus produced, m.p. 131°-132°. [α]_(D) ²⁰ = +56°(chloroform; c = 1%).

EXAMPLE 24

0.86 g. of1β-tert.-butoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-one,dissolved in 10 ml. of dimethoxyethane, is mixed at room temperaturedropwise with a solution of 1.6 ml. of 40% strength peracetic acid in 10ml. of dimethoxyethane. The reaction mixture is worked up as describedin Example 20. After recrystallization from ether, one obtains 0.68 g.of1β-tert.-butoxy-7aβ-methyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-one,m.p. 132°-133°. [α]_(D) ²⁰ = +57° (Chloroform, C =1%).

EXAMPLE 25

0.86 g. of1β-tert.-butoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-oneis dissolved in 20 ml. of dimethoxyethone, and 4 ml. of Jones reagent(8N chromium(VI) oxide solution in dilute sulfuric acid) is addedthereto in two portions. The yellow mixture is distributed between waterand chloroform, and the chloroform phase is extracted with aqueoussodium bicarbonate solution and saturated sodium chloride solution,dried, and evaporated. After recrystallization from ether, 0.56 g. of1β-tert.-butoxy-7aβ-methyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydronindan-5-oneis produced, m.p. 132°-133°.

EXAMPLE 26

0.34 g. of1β-tert.-butoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydronidan-5-oneis dissolved in 5 ml. of dimethoxyethane, and 0.8 g. of lead(IV) oxideand 0.5 ml. of 70% perchloric acid are added thereto. The suspension isagitated for one hour at room temperature, filtered off from theundissolved substance, and the filtrate is worked up as described inExample 20. The yield of1β-tert.-butoxy-7aβ-methyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-oneis 0.31; g.; m.p. 131°-133°.

EXAMPLE 27

A mixture of 3.12 g. of1β-acetoxy-7aβ-methyl-5,6,7,7a-tetrahydroindan-5-one, 1.2 g. ofparaformaldehyde, 2.5 ml. of thiophenol, and 6 ml. of triethanolamine isheated for 2 hours to 110°. After cooling the reaction mixture, it istaken up in chloroform, extracted with 2N aqueous sodium hydrogensolution and water, the organic phase is dried, and the solvent isdistilled off, thus obtaining 5.0 g. of a yellow oil. The latter ischromatographed on silica gel by means of hexane-ethyl acetategradients, thus producing 3.6 of1β-acetoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-oneas an oil. [α]_(D) ²⁰ = +24° (chloroform; c = 1%). IR bands at 5.8, 6.0,7.6, and 8.8 μ.

EXAMPLE 28

2.0 g. of1ε-acetoxy-7aε-methyl-4-(phenylthiomethyl)5,6,7,7a-tetrahydroindan-5-oneis dissolved in 25 ml. of dimethoxyethane; at 5°-10°, a solution of 1.5ml. of 40% peracetic acid in 5 ml. of dimethoxyethane is added thereto.The reaction mixture is worked up as described in Example 20, and alight-yellow oil is thus isolated which is chromatographed on silica gelby means of hexane-ethyl acetate gradients. The result is 1.4 g.of1β-acetoxy-7aβ-methyl4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-onein the form of an oil. [α]_(D) ²⁰ = +13° (chloroform; c = 1%). IR bandsat 5.8, 6.0, 7.6, and 8.8 μ.

EXAMPLE 29

500 mg. of1β-hydroxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-oneis dissolved in 10 ml. of dimethoxyethane and mixed, at roomtemperature, with 1.1 ml. of 40% peracetic acid in 5 ml. ofdimethoxyethane. The reaction mixture is worked up as described inExample 20, thus obtaining, after recrystallization from ether, 420 mg.of1β-hydroxy-7aβ-methyl4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-one,m.p. 125°-126°. [α]_(D) ²⁰ = +72° (chlorform; c = 1%).

EXAMPLE 30

0.45 g. of1β-tert.-butoxy-7aβ-methyl-4-(hexylthiomethyl)-5,6,7,7a-tetrahydronindan-5-oneis dissolved in 10 ml. of dimethoxyethane, and 0.8 ml. of 40% peraceticacid in 5 ml. of dimethyoxyethane, and 0.8 ml. of 40% peracetic acid in5 ml. of dimethoxyethane is added thereto at room temperature. Themixture is worked by analogously to Example 20, thus isolating, afterrecrystallization from hexane, 0.42 g. of1β-tert.-butoxy-7aβ-methyl-4-(hexylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-one,m.p. 51°54.5°. [α]_(D) ²⁰ = +22° (chloroform; c =0 1%).

EXAMPLE 31

93 mg. of 1β-trimethylacetoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-one isdissolved in 2 ml. of dimethoxyethane; at room temperature, 0.3 ml. of40% peracetic acid in 2 ml. of dimethoxyethane is added thereto. Thereaction mixture is worked up as set forth in Example 20, thusproducing, after recrystallization from ether, 80 mg. of1β-trimethylacetoxy-7aβ-methyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-one,m.p. 158°-159°.

EXAMPLE 32

1.32 g. of 1,1-(2',2'-dimethylpropylenedioxy)-8aβ-methyl-1,2,3,4,8,8a-hexahydro-6[7H]-naphtalenone,0.6 ml. of phenyl mercaptan, and 0.15 g. of paraformaldehyde are heatedin 2 ml. of triethanolaine to 110° for 16 hours. The reaction mixture isworked up and chromatographed in accordance with Example 2. From 2.0 g.of a crude product, one obtains 1.23 g. of pure1,1-(2',2'-dimethypropylenedioxy)-8aβ-methyl-5-(phenyltiomethyl)1,2,3,4,8,8a-hexahydro-6[7H]-npthalenone.ε₂₄₅ = 11,000. IR band at 6.0 μ.

EXAMPLE 33

193 mg. of1,1-(2',2'-dimethylpropylenedioxy)-8aβ-methyl-5-(phenylthiomethyl)-1,2,3,4,8,8a-hexahydro-6[7H]naphthalenoneis dissolved in 4 ml. of dimethoxyethane, and 0.6 ml. of 40% peraceticacid in 2 ml. of dimethoxyethane is added thereto at room temperature.The mixturee is worked up as described in Example 24, thus obtaining,after recrystallization from ethyl acetate, 120 mg.1,1-(2',2'-dimethylpropylenedioxy)-8aβ-methyl-5-(phenylsulfonylmethyl)-1,2,3,4,8,8a-hexahydro-6[7H]-naphthalenone,m.p. 220°-222°. [λ ]_(D) ²⁰ = -8° (chloroform; C = 1%).

EXAMPLE 34

290 mg. of1,1-(2',2'-dimethylpropylenedioxy)-7aβ-ethyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindam-5-oneis dissolved in 5 ml. of dimethoxyethane, and 0.7 ml. of 40% peraceticacid in 2 ml. of dimethoxyethane is added thereto. After the reactionmixture has been worked up as described in Example 20, recrystallizationfrom diisopropyl ether yields 190 mg. of1,1-(2',2'-dimethylpropylenedioxy)-7aβ-ethyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-one,m.p. 178°-180°.

EXAMPLE 35

0.56 g. of 1β-tert.-butoxy-7aβ-methyl-5,6,7,7a-tetrahydroindan-5-one,0.44 g. of phenylhydroxymethylsulfone, and 2 ml. of triethanolamine areheated under agitation and in a nitrogen atmosphere to 100° for 16hours. After cooling, the reaction mixture is distributed between etherand water, the ether phase is dried, and the solvent is evaporated underthe vacuum. The residue is chromatographed on silica gel withhexane-ethyl acetate gradients, and, after recrystallization from ether,0.24 g. of1β-tert.-butoxy-7aβ-methyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-oneis obtained, m.p. 133°-134°.

[α ]_(D) ²⁰ = +56° (chloroform; c = 1%).

EXAMPLE 36

0.52 g. of 1β-acetoxy-7aβ-methyl-5,6,7,7-tetrahydroindan-5-one, 0.44 g.of phenylhydroxymethylsulfone, and 2 ml. of triethanolamine aredissolved in 2 ml. of dimethylformamide and the mixture is agitatedunder a nitrogen atmosphere at 110° for 2 hours. Then, the mixture isworked up as described in Example 35, thus obtaining, afterchromatography, 0.35 g. of1β-acetoxy-7β-methyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-oneas an oil. [α ]_(D) ²⁰ = -19° (chloroform; c = 1%).

EXAMPLE 37

0.36 g. of1β-tert.-butoxy-7aβ-methyl-4-(phenylsulfinylmethyl)-5,6,7,7a-tetrahydroindan-5-oneis dissolved in 3 ml. of dimethoxyethane. A solution of 0.5 ml. of ethylacetoacetate and 50 mg. of sodium hydride in 2 ml. of dimethoxyethane isadded to the reaction mixture and the latter is agitated for one hour at20° and for 2 hours at 50° under a nitrogen atmosphere. This solution istaken up in ether and washed out with saturated sodium chloridesolution. After removing the solvent by evaporation, one obtains 0.32 g.of1β-tert.-butoxy-7aβ-methyl-4-(3'-oxo-2'-ethoxycarbonylbutyl)-5,6,7,7a-tetrahydroindan-5-onein the form of an oil. [α ]_(D) ²⁰ = 0° (chloroform; c = 1%). IR bandsat 5.75, 5.80, and 6.0 μ.

EXAMPLE 38

0.38 g. of1β-tert.-butoxy-7aβ-methyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-oneand 0.5 ml. of diethyl malonate are dissolved in 5 ml. ofdimethoxyethane, and 50 mg. of sodium hydride is added thereto. Under anitrogen atmosphere, the reaction mixture is stirred for one hour at 20°and for one-half hour at 50°. After working the reaction mixture up asdescribed in Example 37, 0.35 g. of1β-tert.-butoxy-7aβ-methyl-4-(2',2'-bisethoxycarbonylethyl)-5,6,7,7a-tetrahydroindan-5-oneis obtained as an oil. [α]_(D) ²⁰ = +22° (chloforom; c = 1%). IR bandsat 5.75 and 6.0 μ.

EXAMPLE 39

0.73 g. of1β-acetoxy-7aβ-methyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-oneand 1 ml. of ethyl acetoacetate are dissolved in 5 ml. ofdimethoxyethane and mixed with 100 mg. of sodium hydride. This solutionis agitated for 2 hours at room temperature under nitrogen, and, afterworking the reaction mixture up as described in Example 31, 0.62 g. of1β-acetoxy-7aβ-methyl-4-(3'-oxo-2'-ethoxycarbonylbutyl)-5,6,7,7a-tetrahydroindan-5-oneis obtained in the form of an oil. IR bands at 5.75, 5.80, and 6.0 μ.

EXAMPLE 40

0.38 g. of1β-tert.-butoxy-7aβ-methyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-one,0.20 g. of 2-methyl acetoacetate, and 25 mg. of sodium hydride aredissolved in 5 ml. of dimethoxyethane and agitated for 2 hours at 20°and another 2 hours at 50° under a nitrogen atmosphere. The solution isworked up as set forth in Example 37, thus obtaining 0.34 g. of1β-tert.-butoxy-7aβ-methyl-4-(3'-oxo-2'-methyl-2'-ethoxycarbonylbutyl)-5,6,7,7a-tetrahydroindan-5-oneas an oil.

[α]_(D) ²⁰ = +48° (chloroform; c = 1%), IR bands at 5.75, 5.80, and 6.0μ.

EXAMPLE 41

0.38 g. of1β-tert.-butoxy-7aβ-methyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-one,0.30 g. of 7-chloro-3-oxo-6-octylenic acid ethyl ester, and 25 mg. ofsodium hydride are dissolved in 5 ml. of dimethoxyethane and agitatedfor 2 hours at 20° and another 2 hours at 50° under a nitrogenatmosphere. The reaction mixture is worked up as disclosed in Example37, thus obtaining 0.41 g. of1β-tert.-butoxy-7aβ-methyl-4-(7'-chloro-3'-oxo-2'-ethoxycarbonyl-6'-octenyl)-5,6,7,7a-tetrahydroindan-5-onein the form of an oil.

[α]_(D) ²⁰ = +13° (chloroform; c = 1%). IR bands at 5.75, 5.82, and 6.0μ.

EXAMPLE 42

0.38 g. of1β-tert.-butoxy-7aβ-methyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-one,0.30 g. of 7,7-ethylenedioxy-3-oxooctanoic acid ethyl ester, and 25 mg.of sodium hydride are dissolved in 5 ml. of dimethoxyethane, and thesolution is agitated under a nitrogen atmosphere for 2 hours at 20° andfor another 2 hours at 50°. After the reaction mixture has been workedup as set forth in Example 37, 0.42 g. of1β-tert.-butoxy-7aβ-methyl-4-(7',7'-ethylenedioxy-3'-oxo-2'-ethoxycarbonyloctyl)-5,6,7,7a-tetrahydroindan-5-oneis obtained as an oil. [α]_(D) ²⁰ = +6° (chloroform; c = 1%). IR bandsat 5.76, 5.80, and 6.0 μ.

EXAMPLE 43

2.1 g. of 80% sodium hydride is freed of any oil under a nitrogenatmosphere by washing with anhydrous pentane and then dried undervacuum. Absolute dimethyl sulfoxide (40 ml.) is added under nitrogendropwise to the reaction medium, and the mixture is heated for 2.5 hoursunder agitation to 60°-65°. The solution is diluted with 15 ml. ofabsolute tetrahydrofuran and mixed, at 5°-10° , with 7.5 g. of distilledethyl ester of 5,5-phenylenedioxyhexanoic acid in 15 ml. of absolutetetrahydrofuran. The mixture is agitated for 30 minutes at 20° and for30 minutes at 50°, then cooled in an ice bath, and water is addedthereto. By the use of aqueous hydrochloric acid, the mixture isacidified to a pH of 3-4, the mixture is extracted with chloroform, thechlorofrom phase is washed with water, dried, and evaporated undervacuum. The crude product is filtered over a small amount of silica gel,eluting impurities with hexane-ethyl acetate 1:1, and the desiredcompound with methanol. After recrystallization from diisopropyl ether,5.4 g. of methyl-(6,6-phenylenedioxy-2-oxo-heptyl)-sulfoxide isobtained, m.p. 69° - 70.5°.

0.38 g. of1β-tert.-butoxy-7aβ-methyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-one,0.35 g. of methyl-(6,6-phenylenedioxy-2-oxoheptyl)-sulfoxide, and 25 mg.of sodium hydride are dissolved in 5 ml. of dimethoxyethane, and thesolution is agitated under nitrogen for one hour at room temperature andfor another 2 hours at 50°. After the reaction mixture has been workedup as described in Example 37, 0.45 g. of1β-tert.-butoxy-7aβ-methyl-4-(7',7'-phenylenedioxy-3'-oxo-2'-methylsulfinyloctyl)-5,6,7,7a-tetrahydroindan-5-oneis obtained. IR bands at 5.80, 6.0, 6.75, 8.1, and 9.7-9.8 μ.

EXAMPLE 44

A solution of 0.29 g. ofmethyl-(6,6-phenylenedioxy-2-oxoheptyl)-sulfoxide in 5 ml. ofdimethoxyethane is mixed, at room temperature, with 0.45 ml. of 40%peracetic acid. Then, the reaction mixture is taken up in water andchloroform, the organic phase is separated, washed with aqueous sodiumbicarbonate solution, dried over sodium sulfate, and concentrated undervacuum. The residue is recrystallized from diisopropyl ether, resultingin 0.25 g. of methyl-(6,6-phenylenedioxy-2-oxoheptyl)-sulfone, m.p.70°-71°.

A solution of 0.38 g. of1β-tert.-butoxy-7aβ-methyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-one,0.40 g. of methyl-(6,6-phenylenedioxy-2-oxoheptyl)-sulfone, and 25 mg.of sodium hydride in 5 ml. of dimethoxyethane is agitated for one hourat room temperature and then for 2 hours at 50°. The reaction mixture isworked up as described in Example 37, thus obtaining 0.43 g. of1β-tert.-butoxy-7aβ-methyl-4--(7',7'-phenylenedioxy-3'-oxo-2'-methylsulfonyloctyl)-5,6,7,7a-tetrahydroindan-5-oneas an oil. [α]_(D) ²⁰ = +17° (0.45% in chloroform).

EXAMPLE 45

130 mg. of a 55% sodium hydride - oil dispersion is washed free of oilwith absolute dimethoxyethane, mixed with 1.4 g. of phenylnitromethane,and introduced into a solution of 1.0 g. of1β-acetoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-onein 15 ml. of dimethoxyethane. The mixture is heated for 24 hours underreflux, allowed to cool, and diluted with 10 ml. of chloroform. Then,the reaction mixture is washed in 1N sodium hydroxide solution andwater; the organic phase is dried and concentrated under vacuum. Theproduct thus obtained is 1.0 g. of6-nitro-17β-acetoxy-9,10-seco-1,3,5(10),8(14)-estratetraen-9-one in theform of an oil. IR bands at 5.75, 6.0, 6.4, and 7.3 μ. [α ]_(D) ²⁰ =-7.1° (chloroform; c = 1%).

EXAMPLE 46

470 mg. of a 55% sodium hydride - oil dispersion is washed free of oilwith absolute dimethoxyethane, mixed with 8.8 g. of the ethyl ester ofm-methoxyphenylacetic acid, and added to a solution of 3.3 g. of1β-acetoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-one.The mixture is heated under reflux for 16 hours and worked up asdescribed in Example 45. The thus-obtained crude product is purified bypreparative thinlayer chromatography, thus resulting in 1.7 g. of3-methoxy-17β-acetoxy-6-ethoxycarbonyl-9,10-seco-1,3,5(10),8(14)-estratertraen-9-oneas an oil. IR bands at 5.75 and 6.0 μ. [α]_(D) ²⁰ = +11.5° (chloroform;c = 1%).

EXAMPLE 47

140 mg. of sodium hydride - oil dispersion is mixed in 5 ml. oftetrahydrofuran with 2.2 g. of the ethyl ester of m-methoxyphenylaceticacid and added to a solution of 1.0 g. of1β-tert.-butyloxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-onein 10 ml. of tetrahydrofuran. The mixture is heated for 16 hours reflux,worked up as described in Example 45, and 500 mg. of3-methoxy-17β-tert.-butyloxy-6-ethoxycarbonyl-9,10-seco-1,2,5(10),8(14)-estratetraen-9-oneis thus obtained in the form of an oil. IR bands at 5.75 and 6.0 μ.[α]_(D) ²¹ = +35.4° (chloroform; c = 1%).

EXAMPLE 48

2.0 g. of m-methoxybenzylcyanide is reacted, as described in Example 46,with sodium hydride and 1.0 g. of1β-acetoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-one,worked up, and the reaction product thus obtained is 0.58 g. of3-methoxy-17β-acetoxy-6-cyano-9,10-seco1,3,5(10),8(14)-estratetraen-9-oneas an oil. IR bands at 4.45, 5.75, and 6.0 μ. [α]_(D) ²⁰ = +10.2°(chloroform; c = 1%).

EXAMPLE 49

2.0 g. of m-methoxybenzyl cyanide is reacted, as set forth in Example46, with sodium hydride and 1.0 g. of1β-tert.-butyloxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-one,worked up, and the produce is 0.37 g. of3-methoxy17β-tert.-butyloxy-6-cyano-9,10-seco-1,3,5(10),8(14)-estratetraen-9-onein the form of an oil.

IR bands at 4.45 and 6.0 μ. [α]_(D) ²⁰ = +31.9° (chloroform; c = 1%).

EXAMPLE 50

2.0 g. of 3,4-dimethoxybenzyl cyanide is reacted, as disclosed inExample 46, with sodium hydride and 1.0 g. of 1β-acetoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-one, worked up,and 0.48 g. of2,3-dimethoxy-17β-acetoxy6-cyano-9,10-seco-1,3,5(10),8(14)-estratetraen-9-oneis obtained in the form of an oil.

IR bands at 4.45, 5.75, and 6.0 μ. [α]_(D) ²⁰ = +11° (chloroform; c =1%).

EXAMPLE 51

A solution of 0.22 g. of 3,4-dimethoxybenzyl cyanide in 3 ml. ofabsolute dimethoxyethane is mixed with 50 mg. of an 80% sodium hydride -oil dispersion and agitated until cessation of hydrogen evolution. Then,the mixture is mixed with a solution of 0.47 g. of1β-tert.-butyloxy-7aβ-methyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-onein 5 ml. of dimethoxyethane, and agitated for 1.5 hours at roomtemperature.

The reaction mixture is worked up as described in Example 45, thusobtaining 0.21 g. of2,3-dimethoxy-17β-tert.-butyloxy-6-cyano-9,10-seco-1,3,5(10),8(14)-estratetraen-9-oneas an oil. IR bands at 4.45 and 6.0 μ. [α]_(D) ²¹ = +23° (chloroform; c= 1%).

EXAMPLE 52

The reaction described in Example 51 can also be conducted with the useof1β-tert.-butyloxy-7aβ-methyl-4-(phenylsulfinylmethyl)-5,6,7,7a-tetrahydroindan-5-onein place of1β-tert.-butyloxy-7aβ-methyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-one,if the reaction time is extended to 4 hours.

EXAMPLE 53

A solution of 0.71 g. of 3,5-dimethoxyphenylacetic acid methyl ester and0.13 g. of 80% sodium hydride - oil dispersion in 6 ml. of absolutedimethoxyethane is mixed with 1.27 g. of1β-tert.-butyloxy-7aβ-methyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetahydroindan-5-one-- dissolved in 15 ml. of absolute dimethoxyethane -- and the mixture isagitated for 2 hours at room temperature. Then, the reaction mixture isworked up as described in Example 45, thus obtaining 0.46 g. of1,3-dimethoxy-17β-tert.-butyloxy-6-methoxycarbonyl-9,10-seco-1,3,5(10),8(14)-estratetraen-9-one.IR bands at 5.75 and 6.0 μ.

EXAMPLE 54

A solution of 0.67 g. of 3,5-dimethoxybenzyl cyanide and 150 mg. of 80%sodium hydride - oil dispersion is added to 1.41 g. of1β-tert.-butyloxy-7aβ-methyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-one-- dissolved in 15 ml. of dimethoxyethane -- and the reaction mixture isagitated for 2 hours at room temperature.

The mixture is worked upas described in Example 52, thus producing 0.74g. of1,3-dimethoxy-17β-tert.-butyloxy-6-cyano-9,10-seco-1,3,5(10),8(14)-esratetraen-9-oneas an oil. IR bands at 6.0, 6.2, and 6.8 μ. [α]_(D) ²⁰ = +51°(chloroform; c = 1%).

EXAMPLE 55

Under a nitrogen atmosphere, a mixture of 1.11 g. of1β-acetoxy-8aβ-methyl-1,2,3,4,8,8a-hexahydro-6[7H]-naphthalenone, 0.6ml. of thiophenol, 0.15 g. of paraformaldehyde, and 2 ml. oftriethanolamine is heated to 110° for 2 days. The mixture is thenallowed to cool and poured into 5 ml. of 2N sodium hydroxide solution,thereafter extracted with chloroform, and the chloroform phase iswashed, dried, and concentrated under vacuum. The residue ischromatographed over silica gel, thus obtaining 0.82 g. of1β-acetoxy-8aβ-methyl-5-(phenylthiomethyl)-1,2,3,4,-8,8a-hexahydro-687H]-naphthalenone as an oil.

EXAMPLE 56

0.75 g. of1β-acetoxy-8aβ-methyl-5-(phenylthiomethyl)-1,2,3,4,8,8a-hexahydro-6[7H]-naphthalenoneis dissolved in 10 ml. of dimethoxyethane, mixed with 1 ml. of 40%peracetic acid, and stored for 10 minutes at room temperature. Then, thereaction mixture is diluted with chloroform, washed with sodiumbicarbonate solution, dried, and concentrated under vacuum. The residueis recrystallized from ether, thus producing 0.39 g. of1β-acetoxy-8aβ-methyl-5-(phenylsulfonylmethyl)-1,2,3,4,8,8a-hexahydro-6[7H]-naphthalenone,m.p. 97°-98°.

EXAMPLE 57

150 mg. of 3-methoxybenzoyl cyanide, 40 mg. of 80% sodium hydride - oildispersion, and 0.38 g. of1β-acetoxy-8aβ-methyl-5-(phenylsulfonylmethyl)-1,2,3,4,8,8a-hexahydro-6[7H]-naphthalenoneare reacted as described in Example 51 and worked up, thus obtaining 82mg. of3-methoxy-17aβ-acetoxy-6-cyano-9,10-seco-D-homo-1,3,5(10),8(14)-estratetraen-9-oneas an oil. IR bands at 5.75, 6.0, 6.2, and 6.8 μ.

EXAMPLE 58

1.18 g. of 1β-tert.-butyloxy-7aβ-ethyl-5,6,7,7a-tetrahydroindan-5-one ismixed with 0.15 g. of paraformaldehyde, 0.6 ml. of thiophenol, and 2 ml.of triethanolamin and heated under nitrogen to 90° for 12 hours. Then,another 0.6 ml. of thiophenol and 0.15 g. of paraformaldehyde are addedto the mixture and the latter heated for another 5 hours to 90°.

The reaction mixture is worked up as described in Example 55, and thethus-obtained crude product is purified by chromatography, resulting in1.05 g. of1β-tert.-butyloxy-7aβ-ethyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-onein the form of an oil. [α]_(D) ²⁰ = +26° (chloroform; c = 1%).

EXAMPLE 59

0.85 g. of1β-tert.-butyloxy-7aβ-ethyl-4(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-oneis oxidized as described in Example 56, thus obtaining 0.48 g. of1β-tert.-butyloxy-7aβ-ethyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-one,m.p. 128°. [α]_(D) ²⁰ = +42° (chloroform; c = 1%).

177 mg. of 3,5-dimethoxybenzyl cyanide, 40 mg. of 80% sodium hydride -oil dispersion, and 0.39 g. of1β-tert.-butyloxy-7aβ-ethyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-oneare reacted as described in Example 51 worked up, and the resultantproduct is 63 mg. of1,3-dimethoxy-17β-tert.-butyloxy-18-methyl-9,10-seco-1,3,5(10),8(14)-estratetraen-9-oneas an oil. IR bands at 6.0, 6.2, and 6.8 μ. [α]_(D) ²⁰ = +33°(chloroform; c = 1%).

EXAMPLE 60

0.67 g. of1β-acetoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-oneis reacted, as described in Example 45, with 2.0 g. ofbenzylmethylsulfone and 100 mg. of 50% sodium hydride - oil dispersion,and then worked up, thus obtaining 67 mg. of17β-acetoxy-6-methyl-sulfonyl-9,10-seco-1,3,4(10),-8(14)-estratetraen-9-one.[α]_(D) ²⁰ = +23° (chloroform; c = 1%). IR bands at 5.75, 6.0, 7.65, and8.7 μ.

EXAMPLE 61

A boiling solution of 15.1 g. of 3-methoxybenzaloxime, 2.0 g. of urea,98 g. of disodium hydrogen phosphate dihydrate in 200 ml. ofacetonitrile is mixed within 75 minutes with a solution of 6.4 ml. of77% hydrogen peroxide and 34 ml. of trifluoroacetic anhydride in 50 ml.of acetonitrile. Then, the mixture is heated under reflux for anotherhour, allowed to cool, and poured into 400 ml. of water and extractedwith methylene chloride. The methylene chloride phase is washed, dried,and concentrated to dryness under vacuum. The residue is chromatographedvia a silica gel column, thus producing 6.3 g. of3-methoxyphenylnitromethane as an oil.

1.0 g. of1β-acetoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-oneis reacted, as described in Example 45, with 1.5 g. of3-methoxyphenylnitromethane and 145 mg. of 50% sodium hydride - oildispersion, and worked up, thus obtaining 0.82 g. of3-methoxy-17β-acetoxy-6-nitro-9,10-seco-1,3,5(10),8(14)-estratetraen-9-one.IR bands at 5.75, 6.0, 6.4, and 7.3 μ. [α]_(D) ²⁰ = -22° (chloroform; c= 1%).

EXAMPLE 62

2,0 g of 3,5-dimethoxyphenyl-acetone and 100 mg of a 80 %sodium-hydride-oil dispersion in 10 ml absolute toluol is mixed with asolution of 3,76 g1β-tert.-butyloxy-7aβ-methyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindanin 15 ml absolute toluol. The mixture is agitated for 6 hours at 50°.The reaction mixture is worked up as described in example 45, thusobtaining 3,2 g of1,3-dimethoxy-17β-tert.-butoxy-6-acetyl-9,10-seco-1,3,5(10),8(14)-estratetraen-9-oneas an oil.

IR bands at 5,80 and 6,0 μ.

EXAMPLE 63

2,0 g of 3,5-dimethoxyphenyl-acetone, 100 mg of a 80% sodium hydride-oildispersion and 3,62 g1β-acetoxy-7aβ-methyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-oneare reacted as described in example 62 and worked up, thus obtaining 3,0g of1,3-dimethoxy-17β-acetoxy-6-acetyl-9,10-seco-1,3,5(10),8(14)-estratetraen-9-one.

IR bands at 5.75; 5,80 and 6,0 μ.

EXAMPLE 64

1,7 g of 3-methoxyphenyl-nitromethan, 100 mg of a 80% sodium hydride -oil dispersion and 3,76 g of1β-tert.-butoxy-7aβ-methyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahyroindan-5-oneare reacted as described in example 62 and worked up, thus obtaining3-methoxy-17β-tert.-butoxy-6-nitro-9,10-seco-1,3,5(10),8(14)-estratetraen-9-one.

IR bands at 6,0; 6,4 and 7,3 μ.

EXAMPLE 65

0.75 g of18-tert.-butoxy-7aβ-methyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-one,2,0 g of 3-methoxybenzylmethylsulfon and 100 mg of a 50% sodiumhydride-oil dispersion are reacted as described in example 45 and workedup, thus obtaining 320 mg of17β-tert.-butoxy-3-methoxy-6-methylsulfonyl-9,10-seco-1,3,5(10),8(14)-estratetraen-9-one.

IR bands at 6,0; 7,65 and 8,7 μ.

EXAMPLE 66

A mixture of 1,18 g of1β-tert.-butoxy-8aβ-methyl-1,2,3,4,6,7,8,8a-octahydronaphthalene-6-one,0,175 g of paraformaldehyde, 0.90 g of benzenesulfinic acid, 2,4 ml ofN,N,N',N'-tetramethylethylendiamine and 1,6 ml of glacial acetic acid isstirred for 2 days at 70° under nitrogen atmosphere. The reactionmixture is taken up in chloroform, washed with a saturated solution ofsodiumhydrogencarbonate and with 1 n HCl. The organic phase is driedwith sodium sulfate and the solvent removed under vacuum. The yield of2,33 g of the crude product is purified on silica gel by means ofchromatography (benzine/ethyl acetate 95:5 → 50:50). Afterrecristallisation from diisopropylether/hexane 0.452 g of rac.1β-tert.-butoxy-8aβ-methyl-5-(phenylsulfonylmethyl)-1,2,3,4,6,7,8,8a-octahydronaphthalene-6-oneis thus obtained, m.p. 96° - 98°. ε₂₅₂ = 12700.

EXAMPLE 67

A mixture of 1,11 g of 1β-acetoxy-8aβ-methyl-1,2,3,4,6,7,8,8a-octahydronaphthalene-6one, 0,175 g of paraformaldehyde, 0,90 gof benzenesulfinicacid, 2,4 ml of N,N,N',N'-tetramethylethylenediamineand 1,6 ml of glacial acetic acid is stirred for 2 days at 70°, Thereaction mixture is worked up as described in example 66, thus obtaining0,52 g of1β-Acetoxy-8aβ-methyl-5-(phenylsulfonylmethyl)-1,2,3,4,6,7,8,8a-octahydro-naphthalene-6-one.ε₂₅₂ = 12000.

The preceding examples can be replaced with similar sucess bysubstituting the generically and specifically described reactants and/oroperating conditions of this invention for those used in the precedingexamples.

From the foregoing description, one skilled in the art can easilyascertain the essential characteristics of this invention, and withoutdeparting from the spirit and scope thereof, can make various changesand modifications of the invention to adapt it to various usages andconditions.

What is claimed is:
 1. A bicycloalkane of the formula ##STR12## whereinn is 1 or 2, R₁ is alkyl of 1-4 carbon atoms, X is carbonyl,hydroxymethylene, or hydroxymethylene etherified with alkyl, carbocyclicaryl or carbocyclic aralkyl of up to 10 carbon atoms; and Y is --S--R₂,--SO_(m) -R₂, or ##STR13## wherein m is 1 or 2, R₂ is aryl or aralkyl ofup to 12 carbon atoms, R₃ is hydrogen or alkyl of 1-4 carbon atoms, R₄is phenyl or phenyl substituted by alkoxy of 1-4 carbon atoms orbenzyloxy, and Z is nitro, alkanoyl of 2-4 carbon atoms, alkylsulfinylof 1-4 carbon atoms or alkylsulfonyl of 1-4 carbon atoms.
 2. A compoundaccording to claim 1, wherein R₁ is methyl or ethyl.
 3. A compoundaccording to claim 2, wherein n is
 1. 4. A compound according to claim2, wherein Y is --S--R₂ or --SO₂ zz₂.
 5. A compound according to claim4, wherein R₂ is phenyl.
 6. A compound according to claim 3, wherein Xis hydroxymethylene.
 7. A compound according to claim 3, wherein X isalkoxymethylene wherein the alkyl group is of 1 to 4 carbon atoms.
 8. Acompound according to claim 1,1β-tert.-butoxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahyroindan-5-one.9. A compound according to claim 1,1β-hyroxy-7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahyroindan-5-one.10. A compound according to claim 1,7aβ-methyl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindane-1,3-dione. 11.A compound according to claim 1,1β-tert.-butyloxy-7aβ-ethykl-4-(phenylthiomethyl)-5,6,7,7a-tetrahydroindan-5-one.12. A compound according to claim 1,1β-tert.-butyloxy-7aβ-methyl-4-(phenylsulfinylmethyl)-5,6,7,7a-tetrahydroindan-5-one.13. A compound according to claim 1,1β-tert.-butyloxy-7aβ-methyl-4-(phenylsulfonylmethyl)-5,6,7,7a-tetrahydroindan-5-one.14. A compound according to claim 1,1β-hyroxy-7aβ-methyl-4-(phenylsulfonylmethyl)-5,5,7,7a-tetrahydroindan-5-one.